Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma.

Glioblastoma (GBM) is the most aggressive brain tumor, with a median survival of ∼15 months. Targeted approaches have not been successful in this tumor type due to the large extent of intratumor heterogeneity. Mosaic amplification of oncogenes suggests that multiple genetically distinct clones are present in each tumor.

A Quantitative Paradigm for Decision-Making in Precision Oncology.

The complexity and variability of cancer progression necessitate a quantitative paradigm for therapeutic decision-making that is dynamic, personalized, and capable of identifying optimal treatment strategies for individual patients under substantial uncertainty. Here, we discuss the core components and challenges of such an approach and highlight the need for comprehensive longitudinal clinical and molecular data integration in its development. We describe the complementary and varied roles of mathematical modeling and machine learning in constructing dynamic optimal cancer treatment strategies and highlight the potential of reinforcement learning approaches in this endeavor.

Mutation rate variability as a driving force in adaptive evolution.

Mutation rate is a key determinant of the pace as well as outcome of evolution, and variability in this rate has been shown in different scenarios to play a key role in evolutionary adaptation and resistance evolution under stress caused by selective pressure. Here we investigate the dynamics of resistance fixation in a bacterial population with variable mutation rates, and we show that evolutionary outcomes are most sensitive to mutation rate variations when the population is subject to environmental and demographic conditions that suppress the evolutionary advantage of high-fitness subpopulations. By directly mapping a biophysical fitness function to the system-level dynamics of the population, we show that both low and very high, but not intermediate, levels of stress in the form of an antibiotic result in a disproportionate effect of hypermutation on resistance fixation.

Accurate mass determinations in decay chains with missing energy.

Many beyond the standard model theories include a stable dark matter candidate that yields missing or invisible energy in collider detectors. If observed at the CERN Large Hadron Collider, we must determine if its mass and other properties (and those of its partners) predict the correct dark matter relic density. We give a new procedure for determining its mass with small error.